Abstract
Kinases and phosphatases regulate mRNA synthesis and processing by phosphorylating and dephosphorylating the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. Fcp1 is an essential CTD phosphatase that preferentially hydrolyzes Ser2-PO4 of the tandem YSPTSPS CTD heptad array. Fcp1 crystal structures were captured at two stages of the reaction pathway: a Mg-BeF3 complex that mimics the aspartylphosphate intermediate and a Mg-AlF4- complex that mimics the transition state of the hydrolysis step. Fcp1 is a Y-shaped protein composed of an acylphosphatase domain located at the base of a deep canyon formed by flanking modules that are missing from the small CTD phosphatase (SCP) clade: an Fcp1-specific helical domain and a C-terminal BRCA1 C-terminal (BRCT) domain. The structure and mutational analysis reveals that Fcp1 and Scp1 (a Ser5-selective phosphatase) adopt different CTD-binding modes; we surmise the CTD threads through the Fcp1 canyon to access the active site.
Original language | English (US) |
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Pages (from-to) | 478-490 |
Number of pages | 13 |
Journal | Molecular Cell |
Volume | 32 |
Issue number | 4 |
DOIs | |
State | Published - Nov 21 2008 |
Externally published | Yes |
Keywords
- PROTEINS
- RNA
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology